This research will develop capillary electrophoresis for studying fundamental interactions in protein biochemistry. Its focus is on "protein charge ladders"--families of proteins prepared by acetylation of lysine amino groups, and that differ in their net charge; these families (the "rungs") of the ladders separate in capillary electrophoresis into a set or regularly spaced peaks on the basis of net charge. Study of the interactions of protein charge ladders with charged ligands, with buffers, and with surfactants gives detailed information about these interactions. Charge ladders were originally developed for studying electrostatic interactions; this work will extend the study to the investigation of hydrophobic interactions. The information developed in this research will help in understanding and manipulating a wide range of fundamental biochemical interactions. The research will also use the techniques of soft lithography to develop new types of microfluidic systems for use in capillary electrophoresis and other fluidic applications. The research will provide understanding useful in rationalizing and predicting interactions between proteins and ligands, and ultimately in the rational design of drugs.